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Background and ObjectivesLimited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM.MethodsThis was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26). qMRI assessments include thigh muscle volume (TMV), inter/intramuscular adipose tissue (IMAT), muscle fat fraction (FF), muscle inflammation (T2 relaxation time), IMAT from T2* relaxation (T2*-IMAT), intermuscular connective tissue from T2* relaxation (T2*-IMCT), and muscle macromolecular structure from the magnetization transfer ratio (MTR). Physical performance assessments include sIBM Physical Functioning Assessment (sIFA), 6-minute walk distance, and quantitative muscle testing of the quadriceps. Correlations were assessed using the Spearman correlation coefficient. Responsiveness was assessed using the standardized response mean (SRM).ResultsAfter 1 year, we observed a reduction in TMV (6.8%, p < 0.001) and muscle T2 (6.7%, p = 0.035), an increase in IMAT (9.7%, p < 0.001), FF (11.2%, p = 0.030), connective tissue (22%, p = 0.995), and T2*-IMAT (24%, p < 0.001), and alteration in muscle macromolecular structure (ΔMTR = −26%, p = 0.002). A decrease in muscle T2 correlated with an increase in T2*-IMAT (r = −0.47, p = 0.008). Deposition of connective tissue and IMAT correlated with deterioration in sIFA (r = 0.38, p = 0.032; r = 0.34, p = 0.048; respectively), whereas a decrease in TMV correlated with a decrease in quantitative muscle testing (r = 0.36, p = 0.035). The most responsive qMRI measures were T2*-IMAT (SRM = 1.50), TMV (SRM = −1.23), IMAT (SRM = 1.20), MTR (SRM = −0.83), and T2 relaxation time (SRM = −0.65).DiscussionProgressive deterioration in muscle quality measured by qMRI is associated with a decline in physical performance. Inflammation may play a role in triggering fat infiltration into muscle. qMRI provides valid and responsive measures that might prove valuable in sIBM experimental trials and assessment of muscle pathologic processes.Classification of EvidenceThis study provides Class I evidence that qMRI outcome measures are associated with physical performance measures in patients with sIBM.

Objective Study was conducted to 3D evaluate skeletal effects of two different intraoral force application systems for treating skeletally growing ClassIII patients(RCT). Material and Methods 33 patients recruited and randomly allocated between three groups: GroupI(n = 11)treated with CS2000(CSgroup/ pulling force), GroupII(n = 11)treated with reversed Forsus Fatigue Resistant(RFgroup/ pushing force) and GroupIII(n = 11)untreated control(negative control). A CBCT taken before treatment(T0) and after gaining a 2mm overjet or after observation period of 6months(T1). Skeletal measurements were assessed and compared between groups. Within group comparisons were done using Wilcoxon Sign Rank test. Results Sagittaly in RFgroup, OLp-Apt increased by3.60mm, OLp-Bpt decreased by-2.50mm and OLp-Pg decreased as well by-2.00mm(P P P

Inclusion body myositis (IBM) is a myopathic condition but in some patients has been associated with an axonal length-dependent polyneuropathy. In this study, we quantified the cross-sectional area of the sciatic and tibial nerves in patients with IBM comparing with Charcot-Marie-Tooth disease type 1A (CMT1A) and healthy controls using magnetic resonance neurography (MRN).MRN of the sciatic and tibial nerves was performed at 3T using MPRAGE and Dixon acquisitions. Nerve cross-sectional area (CSA) was measured at the mid-thigh and upper third calf regions by an observer blinded to the diagnosis. Correlations were performed between these measurements and clinical data.A total of 20 patients with IBM, 20 CMT1A and 29 healthy controls (age- and sex-matched) were studied. Sciatic nerve CSA was significantly enlarged in patients with IBM and CMT1A compared to controls (sciatic nerve mean CSA 62.3 ± 22.9 mmMRN reveals significant hypertrophy of the sciatic and tibial nerves in patients with IBM and CMT1A compared to controls. Further studies are needed to correlate with neurophysiological measures and assess whether this finding is useful diagnostically.

This randomized clinical trial was conducted on female patients in need of extraction of at least of two maxillary first premolars. The sample was divided into three groups; Group I: study group with Anterior retraction hook (ARH) of 9 mm, group II: study group with ARH of 6 mm, group III: study group with ARH of 3mm. Cone beam computed tomography were taken at two-time intervals for the whole sample; T1: Before the onset of en-masse retraction and T2: After the completion of en-masse retraction.Significant reduction in the inclination of anterior teeth as measured to the palatal plane had been recorded in three groups. Significant retraction of crowns and roots of anterior teeth had been recorded in all groups. Significantly lower amount of root movement had been recorded in group 2 and 3 compared to group 1. All groups showed significant intrusive movement with significantly less intrusion movement in group 2 and group 3 compared to group 1.

Objective: Primary objective: To evaluate the effect of Miswak extract varnish on streptococcus mutans (S.mutans) counts in saliva and plaque, gingival bleeding index (GBI) and plaque index (PI) in orthodontic patients. Secondary objective: to suggest an appropriate frequency Miswak varnishes application to produce maximum efficiency. Material and methods: Enrolled patients (n=75) were randomly and equally divided into 3groups. Chlorhexidine varnish group, Miswak varnish group and control group. S.mutans counts in plaque and saliva, GBI and PI were evaluated at different time points; T0: before brackets bonding, T1: two weeks after brackets bonding, T2: one months after brackets bonding and T3: three months after brackets bonding. Results: Both chlorhexidine and Miswak varnishes reduced plaque S.mutans counts significantly at T2 compared to the controls, with no significant difference between Chlorhexidine and Miswak varnishes at this timepoint. After 3 months, chlorhexidine varnish group had the lowest S.mutans plaque counts followed by Miswak varnish group, while the control group had the highest counts. GBI was reduced significantly in both chlorhexidine and Miswak varnishes groups, when compared to the control group at both one month and 3 months timepoints with no statistically significant differences between chlorhexidine and Miswak neither at one month nor at 3 months. PI showed no statistically significant differences between the 3 study groups at different timepoints. Conclusions: Miswak varnish can be an acceptable natural substitute to chlorhexidine varnish as an anticariogenic agent if applied at monthly basis. Mechanical brushing is mandatory to reduce plaque accumulation and maintain proper gingival health.

The aim of this RCT is to study the effect of low level laser therapy (LLLT) with en masse maxillary anterior retraction in class II division 1 female patients on root resorption. Materials and Methods: 20 non-growing female patients were randomly allocated in 2 groups: Group I receiving LLLT 4 times/month (0, 3, 7 and, 14) days of activation, Group II receiving no laser therapy. CBCT was taken at T1 (prior to retraction) and T2 (after closure of spaces). Root resorption was evaluated by analyzing both root length (RL) and root area (RA) of six anterior teeth and compared between T1 and T2. Results: Root resorption was detected in all teeth in both groups with significant difference between the two groups regarding RL and RA (P

The aim of this study was to compare tooth measurements obtained by two differently acquired digital model and conventional plaster cast measurements. Materials and methods: This study comprised 40 patients. Digital casts were obtained by two methods; Intraoral scanning by carestream intraoral scanner CS3600 powder free and model scanning by cast scanner Sirona InEos X5 scanner. Three study groups were obtained; Group 1: conventional dental casts ,group 2: digital casts obtained with powder free intraoral scanning and group 3: digital casts obtained by cast scanner. Intercanine and intermolar widths in addition to individual tooth measurements were made using Viewbox program for digital casts and digital caliper for the plaster cast. Results: No statistical significant difference between three groups regarding all measurements had been found. Conclusion:The results of this study confirm the potential of intraoral scanning to acquire data as accurate as alginate impressions as well as scanned digital casts for orthodontic applications

AIMS: Sudden unexpected death in epilepsy (SUDEP) likely arises as a result of autonomic dysfunction around the time of a seizure. In vivo MRI studies report volume reduction in the medulla and other brainstem autonomic regions. Our aim, in a pathology series, is to correlate regional quantitative features on 9.4T MRI with pathology measures in medullary regions. METHODS: Forty-seven medullae from 18 SUDEP, 18 nonepilepsy controls and 11 epilepsy controls were studied. In 16 cases, representing all three groups, ex vivo 9.4T MRI of the brainstem was carried out. Five regions of interest (ROI) were delineated, including the reticular formation zone (RtZ), and actual and relative volumes (RV), as well as T1, T2, T2* and magnetization transfer ratio (MTR) measurements were evaluated on MRI. On serial sections, actual and RV estimates using Cavalieri stereological method and immunolabelling indices for myelin basic protein, synaptophysin and Microtubule associated protein 2 (MAP2) were carried out in similar ROI. RESULTS: Lower relative RtZ volumes in the rostral medulla but higher actual volumes in the caudal medulla were observed in SUDEP (P

Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery.

ObjectiveIn the pivotal DEFINE and CONFIRM trials for dimethyl fumarate (DMF), patterns of brain volume changes were different, potentially due to low sample sizes and because MRIs were analyzed at two different reading centers. We evaluated effects of DMF on brain volume change in patients with multiple sclerosis (MS) through reanalysis of pooled images from DEFINE/CONFIRM trials in one reading center.MethodsMRIs from DEFINE/CONFIRM at weeks 0, 24, 48, and 96 from patients randomized to twice-daily DMF or placebo (PBO) were reanalyzed at the Cleveland Clinic to measure brain parenchymal fraction (BPF). To account for pseudoatrophy, brain volume estimates were re-baselined to calculate changes for weeks 48–96.ResultsAcross studies, 301 and 314 patients receiving DMF and PBO, respectively, had analyzable MRIs. In weeks 0–48, mean ± SE percentage change in BPF was −0.44 ± 0.04 vs. −0.34 ± 0.04% in DMF vs. PBO, respectively, whereas in weeks 48–96, mean ± SE percentage change in BPF was −0.27 ± 0.03 vs. −0.41 ± 0.04% in DMF vs. PBO, respectively. The mixed-effect model for repeated measures showed similar results: in weeks 48–96, estimated change (95% confidence interval) in BPF was −0.0021 (−0.0027, −0.0016) for DMF vs. −0.0033 (−0.0039, −0.0028) for PBO (35.9% reduction; p = 0.0025).ConclusionsThe lower rate of whole brain volume loss with DMF in this pooled BPF analysis in the second year vs. PBO is consistent with its effects on relapses, disability, and MRI lesions. Brain volume changes in the first year may be explained by pseudoatrophy effects also described in other MS clinical trials.

We investigated the associations between Apolipoprotein E (APOE) genotype, intracerebral haemorrhage (ICH) and neuroimaging markers of cerebral amyloid angiopathy (CAA).We included patients from a prospective, multi-centre UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed association of APOE genotype with ICH (compared to controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with haematoma location (lobar or deep) and brain computed tomography (CT) markers of CAA (finger like projections [FLP] and subarachnoid extension [SAE]).We included 907 patients with ICH and 2636 controls. Mean age was 73.2 (12.4 SD) years for ICH cases vs. 69.6 (0.2 SD) for population controls; 50.3% of cases and 42.1% of controls were female. Compared to controls, APOE ε2 allele was associated with all (lobar and non-lobar) as well as lobar ICH on its own in the dominant model, i.e. any APOE ε2 allele (OR 1.38, 95%CI 1.13-1.7, p=0.002 and OR 1.50, 95%CI 1.1-2.04, p=0.01, respectively), but not deep ICH in an age-adjusted analyses (OR 1.26, 95%CI 0.97-1.63, p=0.08) compared to controls. In the cases only analysis, APOE ε4 allele was associated with lobar compared to deep ICH in an age-adjusted analyses (OR 1.56, 95%CI 1.1-2.2, p=0.01). When assessing CAA markers, APOE alleles were independently associated with FLP (ε4: OR 1.74, 95%CI 1.04-2.93, p=0.04 and ε2/ε4: 2.56, 95%CI 0.99-6.61, p=0.05). We did not find an association between APOE alleles and SAE.We confirmed associations between APOE alleles and ICH including lobar ICH. Our analysis shows selective associations between APOE ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different APOE alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH.

Introduction:Failure of orthodontic bonded retainers may affect the orthodontic results and cause relapse.Objectives:To compare in vitro the effect of vertical load on failure of three different bonded lingual retainers:Flat braided wire “Bond A. Braid”, Dead soft wire “RESPOND”, Fiber reinforced composite “Infibra Ribbon”. Bonded with Tetric-N Flowadhesive system.Materials and Methods:Ninetymandibular incisors were used in the study, thirty specimens (N=30) in triads divided into 3 groups (n=10 for each group). Roots of the incisors were covered with elastomeric impression material to mimic periodontal ligaments elasticity and embedded in triads in acrylic resin blocks. They were randomly divided into 3 groups to receive the following retainer wire materials:Group A (Flat braided wire “Bond A. Braid”), Group B (Dead soft wire “RESPOND”), and Group C (Fiber reinforced composite “Infibra Ribbon”). And these retainer wires were bonded to the lingual surfaces using Tetric-N Flowadhesive system.The three groups were subjected to 10,000 thermal cycles between 55▫C & 5▫C using a thermo-cycling machine. Each specimen was subjected to loading forces at the incisal edge of the middle incisor for 125,000 cycles. Then failure forces were measured using a Universal Testing Machine at a cross head speed (1mm/min) applied on the wire of the interproximal segments.Failure sites were determined and the adhesive remnant index (ARI) was observed using a stereomicroscope at (×20) magnification.Results:Mean debonding forces were 46.27 ±12.28, 36.03 ± 6.09, 30.09 ± 15.73 N for Groups A,B and C respectively, presenting significant difference between the groups (p < 0.05). The highest value for the mean force was found for the Bond-A-Braid (group A) and the lowest value for the mean force was found for the FRC (group C). There was no statistically significant difference in displacement among test groups. There was no fracture occurred of any wire. There was no significant difference between the distribution of the ARI score between the three groups (p=0.322).The ARI scores were observed under the optical stereomicroscope showing multiple failures at the composite-wire interface and the tooth-composite interface.Conclusions: There was a significant difference between “Bond A. Braid” wire and “FRC” where “Bond A. Braid” had the highest debonding forces and the “FRC” had the lowest debonding forces. There was no significant difference in displacement of the retainers between the three groups. There was no significant difference between the ARI of the lingual retainer systems and types of failure as well.

Nowadays, several new global trends have emerged, empathizing urban design dimension in the planning of transportation networks and keeping pace with urban, environmental and social development. These trends emerged into practice in many developed countries, aiming at achieving sustainability, improving the built environment, reducing and addressing the environmental impacts resulted from the misuse of local resources of the environment, improving public health and providing better quality of life. The patterns of these trends varied in both urban design and urban transportation. The frameworks of both urban design and urban transportation are closely linked to these modern trends, each of which relies on its own practical framework and is adapted to the local conditions according to the type and pattern of urbanization in which these trends originated. It is worth mentioning that the crosscutting points and the linkages between the two areas, urban design and urban transportation, clearly exist in a global methodological frameworks covering the design process in both fields. Hence, the research gap to be covered in this paper is creating a global framework that covers the design process in both fields.The objectives of urban design are closely related to the objectives of urban transportation. This makes it necessary to integrate these two fields in a clear and systematic framework that suits and meets the needs of the urban content of the Egyptian society. Taking into consideration the pace of development taking place in both areas at the global level, and the emergence of many attempts integrating both the theoretical and the operational level. The Egyptian society faces a large gap between the current situation of the Egyptian urbanization and the extent of the application of these modern global trends due to the absence of the importance of integrating urban design dimension in planning urban transportation in existing urban cities.In this context, the paper seeks to reach a comprehensive vision that combines the two fields in order to improve the urban built environment and reduce the problems associated with the urban transportation sector in Egypt with aid of many of the modern global trends that dealt with this subject and reached many solutions that can be adopted in Egypt. The paper adopted the formulation of a generalized framework that includes the dimension of urban design in the planning and design of urban transport networks and included two pillars. (a) Proposing an ideological framework elaborating the integrated design process, which includes the use of the global modern trends in urban design and urban transportation at the functional urban, social, environmental and economic level; (b) Proposing a theoretical phased design process in line with the local Egyptian reality, which includes different application levels for planning, design, management, development and operation.

Background Increased risk of enamel demineralization during and after orthodontic treatment raises the demand for better preventive measures including combinations of laser, CPP-ACP, and fluoride. The combination of Er,Cr:YSGG laser with CPP-ACP was proved to have a synergetic effect compared to each of them alone. Shear bond strength (SBS) of orthodontic brackets bonded to the enamel surface after being treated with preventive measures is critical. The aim of this study was to compare the SBS and failure mode of metallic brackets bonded to teeth with no pretreatment and pretreated enamel surface, either with Er,Cr:YSGG laser alone or combined with CPP-ACP. Methods Sixty sound extracted human premolar teeth were allocated randomly to 3 groups: In Group 1 (control), teeth were etched and bonded directly; in Group 2, laser pretreatment of the enamel surface was done followed by etching and bonding as in the control group; in Group 3, the enamel surface was lased then CPP-ACP was applied according to the manufacturer instructions, etched and bonded. SBS and Adhesive remnant index (ARI) were evaluated. Results No significant differences were found between the 3 groups neither in the SBS nor in the ARI scores. Conclusions The use of combined Er,Cr:YSGG laser with CPP-ACP as a preventive measure before bonding orthodontic brackets does not endanger the bracket’s bonding strength.

ObjectiveTo determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score.MethodsWe included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers.ResultsIn multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12–2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19–2.73), deep atrophy presence (OR 1.66, 95% CI 1.17–2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36–2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68–0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69–0.76). These results were confirmed when lobar and nonlobar ICH were considered separately.ConclusionsThe ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination.Trial Registration InformationClinicalTrials.gov Identifier: NCT02513316.

Background: There is uncertainty about the clinical benefit of admission to critical care after spontaneous intracerebral haemorrhage (ICH). Purpose: We investigated factors associated with critical care admission after spontaneous ICH and evaluated associations between critical care and 6-month functional outcome. Methods: We included 825 patients with acute spontaneous non-traumatic ICH, recruited to a prospective multicenter observational study. We evaluated the characteristics associated with critical care admission and poor 6-month functional outcome (modified Rankin Scale, mRS > 3) using univariable (chi-square test and Wilcoxon rank-sum test, as appropriate) and multivariable analysis. Results: 286 patients (38.2%) had poor 6-month functional outcome. Seventy-seven (9.3%) patients were admitted to critical care. Patients admitted to critical care were younger (p < 0.001), had lower GCS score (p < 0.001), larger ICH volume (p < 0.001), more often had intraventricular extension (p = 0.008) and underwent neurosurgery (p < 0.001). Critical care admission was associated with poor functional outcome at 6 months (39/77 [50.7%] vs 286/748 [38.2%]; p = 0.034); adjusted OR 2.43 [95%CI 1.36–4.35], p = 0.003), but not with death (OR 1.29 [95%CI 0.71–2.35; p = 0.4). In ordinal logistic regression, patients admitted to critical care showed an OR 1.47 (95% CI 0.98–2.20; p = 0.07) for a shift in the 6-month modified Rankin Scale. Conclusions: Admission to critical care is associated with poor 6-month functional outcome after spontaneous ICH but not with death. Patients admitted to critical care were a priori more severely affected. Although adjusted for main known predictors of poor outcome, our findings could still be confounded by unmeasured factors. Establishing the true effectiveness of critical care after ICH requires a randomised trial with clinical outcomes and quality of life assessments.

Objectives At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). Conclusion Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. Key Points • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol. • Perfusion MRI is recommended for diagnosis and follow-up of glioma. • Use of advanced imaging could be promoted with increased education activities. • Most response assessment is currently performed qualitatively. • Reporting templates are not widely used, and could facilitate standardisation. Electronic supplementary material The online version of this article (10.1007/s00330-018-5314-5) contains supplementary material, which is available to authorized users.

Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's di ...

Background Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias. Objective To assess the safety and tolerability of low frequency (20 Hz) NBM DBS in DLB patients and explore its potential effects on both clinical symptoms and functional connectivity in underlying cognitive networks. Methods We conducted an exploratory randomised, double-blind, crossover trial of NBM DBS in six DLB patients recruited from two UK neuroscience centres. Patients were aged between 50 and 80 years, had mild-moderate dementia symptoms and were living with a carer-informant. Patients underwent image guided stereotactic implantation of bilateral DBS electrodes with the deepest contacts positioned in the Ch4i subsector of NBM. Patients were subsequently assigned to receive either active or sham stimulation for six weeks, followed by a two week washout period, then the opposite condition for six weeks. Safety and tolerability of both the surgery and stimulation were systematically evaluated throughout. Exploratory outcomes included the difference in scores on standardised measurements of cognitive, psychiatric and motor symptoms between the active and sham stimulation conditions, as well as differences in functional connectivity in discrete cognitive networks on resting state fMRI. Results Surgery and stimulation were well tolerated by all six patients (five male, mean age 71.33 years). One serious adverse event occurred: one patient developed antibiotic-associated colitis, prolonging his hospital stay by two weeks. No consistent improvements were observed in exploratory clinical outcome measures, but the severity of neuropsychiatric symptoms reduced with NBM DBS in 3/5 patients. Active stimulation was associated with functional connectivity changes in both the default mode network and the frontoparietal network. Conclusion Low frequency NBM DBS can be safely conducted in DLB patients. This should encourage further exploration of the possible effects of stimulation on neuropsychiatric symptoms and corresponding changes in functional connectivity in cognitive networks. Trial registration number NCT02263937.

The chromosome 9 open reading frame 72 (C9orf72) GGGGCC repeat expansion has been associated with several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. It has also been associated with increased white matter changes in frontotemporal dementia and risk of cognitive impairment in ALS. Dementia is common both before and after intracerebral hemorrhage (ICH). Because the mechanisms of cognitive impairment in patients with ICH are uncertain, we investigated whether C9orf72 could influence dementia risk in this patient group. Therefore, we genotyped 1010 clinically characterized ICH cases and 2147 population controls in comparison with prior data of dementia and ALS cases. We did not find any association between C9orf72 repeat expansion and repeat size with ICH compared with controls or with dementia when assessing ICH patients only. The frequency of C9orf72 expansions in our series of individuals born in 1946 (2/2147) and other U.K. controls was age dependent, decreasing with increasing age, highlighting the high age-dependent penetrance of this expansion.

ObjectiveTo summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings.MethodsClinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement.ResultsA wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design.ConclusionsImaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.

Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift fat-water separation with T2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B1 sensitivity of IDEAL-CPMG T2 -water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T2 -water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter-scan interval of 4 weeks using IDEAL-CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T2 -water and the fat signal amplitude muscle regions manually segmented. Overall mean calf-level muscle T2 -water in healthy subjects was 31.2 ± 2.0 ms, without significant inter-muscle differences (p = 0.37). Inter-subject and inter-scan coefficients of variation were 5.7% and 3.2% respectively for T2 -water and 41.1% and 15.4% for f.f. Bland-Altman mean bias and ±95% coefficients of repeatability were for T2 -water (0.15, -2.65, 2.95) ms and f.f. (-0.02, -1.99, 2.03)%. There was no relationship between T2 -water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B1 error or any correlation between T2 -water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T2 -water and f.f. (ρ = 0.59, p

The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours.

Background The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. Aim To assess HLA-DRB * 1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Methods Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB * 1501 haplotype was determined by genotyping (rs3135388). Results No significant differences were observed in MRI measures between the HLA-DRB * 1501 subgroups. Conclusions The HLA-DRB * 1501 haplotype is not strongly associated with MRI-visible grey matter pathology.

Introduction In this study we investigated muscle magnetic resonance imaging in congenital myasthenic syndromes (CMS). Methods Twenty-six patients with 9 CMS subtypes and 10 controls were imaged. T1-weighted (T1w) and short-tau inversion recovery (STIR) 3-Tesla MRI images obtained at thigh and calf levels were scored for severity. Results Overall mean the T1w score was increased in GFPT1 and DPAGT1 CMS. T1w scans of the AChR-deficiency, COLQ, and CHAT subjects were indistinguishable from controls. STIR images from CMS patients did not differ significantly from those of controls. Mean T1w score correlated with age in the CMS cohort. Conclusions MRI appearances ranged from normal to marked abnormality. T1w images seem to be especially abnormal in some CMS caused by mutations of proteins involved in the glycosylation pathway. A non-selective pattern of fat infiltration or a normal-appearing scan in the setting of significant clinical weakness should suggest CMS as a potential diagnosis. Muscle MRI could play a role in differentiating CMS subtypes. Muscle Nerve, 2016

Purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable, immune-mediated condition characterised by progressive or relapsing motor and sensory neurological deficits. The diagnosis is based on a combination of clinical, neurophysiological and supportive criteria, but can be challenging. In this study, we quantified the diameter and cross-sectional area of the lumbosacral nerve roots, and explored the imaging characteristics of the sciatic nerves, in patients with CIDP versus healthy controls using MRI. Methods MRI of the lumbosacral plexus and both thighs was performed at 3 T. Orthogonal diameter and cross-sectional area of the lumbosacral nerve roots were measured, along with sciatic nerve cross-sectional area at the mid-thigh level. The MRI appearance of the sciatic nerves was also evaluated qualitatively. All measurements were performed by an observer blinded to the diagnosis. Results 10 patients with CIDP and 10 healthy controls (age and sex-matched) were studied. Lumbosacral nerve root diameter and cross-sectional area were significantly increased in patients with CIDP compared to controls (mean diameter 6.0 ± 1.1 mm vs 4.8 ± 0.3 mm; p = 0.006), with a high sensitivity (89 %) and specificity (90 %) on ROC analysis. Sciatic nerve cross sectional area was also significantly increased in the CIDP group, and was accompanied by qualitative MRI changes. Conclusions Quantitative MRI reveals significant hypertrophy of the lumbosacral nerve roots and sciatic nerves in patients with CIDP compared to controls. This study provides further evidence for the inclusion of lumbosacral nerve root and sciatic nerve hypertrophy on MRI as a supportive feature in the diagnostic criteria for CIDP.

Background:Autoantibodies directed against cytosolic 5´-nucleotidase 1A (cN1A) have been identified in sporadic inclusion body myositis (sIBM) and other connective tissue diseases. Anti-cN1A antibodies may support the diagnostic process for sIBM as well as potentially provide clues for disease pathogenesis. Nevertheless, the utility of anti-cN1A autoantibody testing in clinical practice remains unclear and requires validation.Objectives:To investigate the association between anti-cN1A antibody status and clinical and MRI features in patients with sIBM.Methods:Data for patients fulfilling European Neuromuscular Centre (ENMC) 2011 criteria for sIBM were obtained from a natural history study database. Demographic, clinical, functional assessment, and muscle MRI data in patients with sIBM who had anti-cN1A autoantibody testing were collected and analysed. Comparisons between subgroups with anti-cN1A antibody status were performed with the Mann-Whitney or Fisher’s exact tests, as appropriate.Results:Forty-nine patients with sIBM had anti-cN1A autoantibody testing, of whom 17 (34.7%) were positive. Twelve patients had muscle MRI performed (seropositivity=5). Demographics, disease duration at antibody testing and overall disease pattern were closely matched in antibody positive and negative cohorts. Dysphagia was more common in the seropositive subgroup (77% vs 47%, p=0.070). Antibody positive patients were more severely affected with a trend to lower IBM functional rating scale (IBMFRS) scores (22.4±8.4 vs 26.7±6.4, p=0.09) with significantly worse ability to climb stairs (0.9±0.9, 1.7±1.1, p=0.02). On T1-weighted MRI more fatty infiltration was found in seropositive patients (Mercuri score: 3.0±0.8 vs 1.7±0.7, p=0.03). Short tau inversion recovery (STIR) hyperintensity was more conspicuous in seropositive patients (STIR extent score: 2.4±0.6 vs 1.4±0.7, p=0.04).Conclusion:There was a trend for more dysphagia and severity of dysphagia in seropositive patients. Differences in upper limb involvement were not seen according to IBMFRS and Medical Research Council (MRC) strength grades. Seropositive patients were more severely affected at the lower limb level, in terms of muscle weakness, physical function, MRI fatty infiltration and muscle inflammation. These results suggest positive antibody status is associated with a worse phenotype. These results have potential implications in clinical trials: whether antibody status influences treatment response should be assessed.Disclosure of Interests:Revadee Dejthevaporn: None declared, Sachit Shah: None declared, Stephen Wastling: None declared, John Thornton: None declared, Tarek Yousry: None declared, Jasper M Morrow: None declared, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB

ObjectivesHereditary sensory neuropathy type 1 (HSN1) is a rare, slowly progressive neuropathy causing profound sensory deficits and often severe motor loss. L-serine supplementation is a possible candidate therapy but the lack of responsive outcome measures is a barrier for undertaking clinical trials in HSN1. We performed a 12-month natural history study to characterise the phenotype of HSN1 and to identify responsive outcome measures.MethodsAssessments included Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), CMTNSv2-Rasch modified, nerve conduction studies, quantitative sensory testing, intraepidermal nerve fibre density (thigh), computerised myometry (lower limbs), plasma 1-deoxysphingolipid levels, calf-level intramuscular fat accumulation by MRI and patient-based questionnaires (Neuropathic Pain Symptom Inventory and 36-Short Form Health Survey version 2 [SF-36v2]).Results35 patients with HSN1 were recruited. There was marked heterogeneity in the phenotype mainly due to differences between the sexes: males generally more severely affected. The outcome measures that significantly changed over 1 year and correlated with CMTNSv2, SF-36v2-physical component and disease duration were MRI determined calf intramuscular fat accumulation (mean change in overall calf fat fraction 2.36%, 95% CI 1.16 to 3.55, p=0.0004), pressure pain threshold on the hand (mean change 40 kPa, 95% CI 0.7 to 80, p=0.046) and myometric measurements of ankle plantar flexion (median change −0.5 Nm, IQR −9.5 to 0, p=0.0007), ankle inversion (mean change −0.89 Nm, 95% CI −1.66 to −0.12, p=0.03) and eversion (mean change −1.61 Nm, 95% CI −2.72 to −0.51, p=0.006). Intramuscular calf fat fraction was the most responsive outcome measure.ConclusionMRI determined calf muscle fat fraction shows validity and high responsiveness over 12 months and will be useful in HSN1 clinical trials.

Author(s): Miller, David H; Lublin, Fred D; Sormani, Maria Pia; Kappos, Ludwig; Yaldizli, Ozgur; Freedman, Mark S; Cree, Bruce AC; Weiner, Howard L; Lubetzki, Catherine; Hartung, Hans-Peter; Montalban, Xavier; Uitdehaag, Bernard MJ; MacManus, David G; Yousry, Tarek A; Gandini Wheeler-Kingshott, Claudia AM; Li, Bingbing; Putzki, Norman; Merschhemke, Martin; Haring, Dieter A; Wolinsky, Jerry S | Abstract: ObjectiveTo investigate the relationship between brain volume and disability worsening over ≥3nyears in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial (nn=n487; clinicaltrials.gov NCT00731692).MethodsMagnetic resonance imaging scans were collected annually. Brain volume loss was determined using SIENA. Patients were stratified by baseline normalized brain volume after adjusting for demographic and disease-burden covariates.ResultsBaseline normalized brain volume was predictive of disability worsening: Risk of 3-month confirmed disability progression was reduced by 36% for high versus low baseline normalized brain volume (Cox's model hazard ratio 0.64, Pn=n0.0339; log-rank test: Pn=n0.0297). Moreover, on-study brain volume loss was significantly associated with disability worsening (Pn=n0.012) and was evident in patients with or without new lesions or relapses. Brain volume loss depended significantly on baseline T2 lesion volume (Pnln0.0001). Despite low inflammatory activity at baseline (13% of patients had gadolinium-enhancing lesions) and throughout the study (mean 0.5 new/enlarging T2 lesions and 172nmm3 T2 lesion volume increase per year), baseline T2 lesion volume was substantial (mean 10ncm3). Lower normalized brain volume at baseline correlated with higher baseline T2 volume and older age (both Pnln0.0001).InterpretationBaseline brain volume and the rate of ongoing brain atrophy are significantly associated with disability worsening in primary progressive multiple sclerosis. Brain volume loss is significantly related to baseline T2 lesion volume, but partially independent of new lesion activity, which might explain the limited efficacy of anti-inflammatory treatment.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using an MRI-guided and MRI-verified technique without microelectrode recording is an effective and safe surgical treatment for patients with Parkinson's disease (PD).To assess the anatomical accuracy of lead placement after MRI-guided, MRI-verified STN DBS using post-mortem histology and high-field MRI at 9.4 T.We conducted post-mortem analysis of a patient's brain who had had MRI-guided, MRI-verified STN DBS for PD, using 9.4-T MRI and histology. After death, the brain was retrieved and a block including the electrode tracks down to the mesencephalon was examined with high-field MRI at 9.4 T and histological analysis.High-field MRI images and corresponding histological examination showed that each electrode track ended within the intended target area, and that DBS did not cause significant neuroparenchymal tissue damage.This study supports the anatomical accuracy of the MRI-guided and MRI-verified method of STN DBS.

The role of MRI in the assessment of multiple sclerosis (MS) goes far beyond the diagnostic process. MRI techniques can be used as regular monitoring to help stage patients with MS and measure disease progression. MRI can also be used to measure lesion burden, thus providing useful information for the prediction of long-term disability. With the introduction of a new generation of immunomodulatory and/or immunosuppressive drugs for the treatment of MS, MRI also makes an important contribution to the monitoring of treatment, and can be used to determine baseline tissue damage and detect subsequent repair. This use of MRI can help predict treatment response and assess the efficacy and safety of new therapies. In the second part of the MAGNIMS (Magnetic Resonance Imaging in MS) network's guidelines on the use of MRI in MS, we focus on the implementation of this technique in prognostic and monitoring tasks. We present recommendations on how and when to use MRI for disease monitoring, and discuss some promising MRI approaches that may be introduced into clinical practice in the near future.

High-resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule-associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood-brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P

00004; International audience; PurposeIntraoperative MRI (iMRI) is a powerful modality for acquiring images of the brain to facilitate precise image-guided neurosurgery. Diffusion-weighted MRI (DW-MRI) provides critical information about location, orientation and structure of nerve fibre tracts, but suffers from the “susceptibility artefact” stemming from magnetic field perturbations due to the step change in magnetic susceptibility at air–tissue boundaries in the head. An existing approach to correcting the artefact is to acquire a field map by means of an additional MRI scan. However, to recover true field maps from the acquired field maps near air–tissue boundaries is challenging, and acquired field maps are unavailable in historical MRI data sets. This paper reports a detailed account of our method to simulate field maps from structural MRI scans that was first presented at IPCAI 2014 and provides a thorough experimental and analysis section to quantitatively validate our technique.MethodsWe perform automatic air–tissue segmentation of intraoperative MRI scans, feed the segmentation into a field map simulation step and apply the acquired and the simulated field maps to correct DW-MRI data sets.ResultsWe report results for 12 patient data sets acquired during anterior temporal lobe resection surgery for the surgical management of focal epilepsy. We find a close agreement between acquired and simulated field maps and observe a statistically significant reduction in the susceptibility artefact in DW-MRI data sets corrected using simulated field maps in the vicinity of the resection. The artefact reduction obtained using acquired field maps remains better than that using the simulated field maps in all evaluated regions of the brain.ConclusionsThe proposed simulated field maps facilitate susceptibility artefact reduction near the resection. Accurate air–tissue segmentation is key to achieving accurate simulation. The proposed simulation approach is adaptable to different iMRI and neurosurgical applications.

Background: In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. Objective: To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Methods: Seventy-two people with MS (46 relapsing–remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Results: Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Conclusion: Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability.

Subjects with Duchenne Muscular Dystrophy (DMD) suffer from progressive muscle damage leading to diaphragmatic weakness that ultimately requires ventilation. Emerging treatments have generated interest in better characterizing the natural history of respiratory impairment in DMD and responses to therapy. Dynamic (cine) Magnetic Resonance Imaging (MRI) may provide a more sensitive measure of diaphragm function in DMD than the commonly used spirometry. This study presents an analysis pipeline for measuring parameters of diaphragmatic motion from dynamic MRI and its application to investigate MRI measures of respiratory function in both healthy controls and non-ambulant DMD boys. We scanned 13 non-ambulant DMD boys and 10 age-matched healthy male volunteers at baseline, with a subset (n = 10, 10, 8) of the DMD subjects also assessed 3, 6, and 12 months later. Spirometry-derived metrics including forced vital capacity were recorded. The MRI-derived measures included the lung cross-sectional area (CSA), the anterior, central, and posterior lung lengths in the sagittal imaging plane, and the diaphragm length over the time-course of the dynamic MRI. Regression analyses demonstrated strong linear correlations between lung CSA and the length measures over the respiratory cycle, with a reduction of these correlations in DMD, and diaphragmatic motions that contribute less efficiently to changing lung capacity in DMD. MRI measures of pulmonary function were reduced in DMD, controlling for height differences between the groups: at maximal inhalation, the maximum CSA and the total distance of motion of the diaphragm were 45% and 37% smaller. MRI measures of pulmonary function were correlated with spirometry data and showed relationships with disease progression surrogates of age and months non-ambulatory, suggesting that they provide clinically meaningful information. Changes in the MRI measures over 12 months were consistent with weakening of diaphragmatic and inter-costal muscles and progressive diaphragm dysfunction. In contrast, longitudinal changes were not seen in conventional spirometry measures during the same period. Dynamic MRI measures of thoracic muscle and pulmonary function are, therefore, believed to detect meaningful differences between healthy controls and DMD and may be sensitive to changes in function over relatively short periods of follow-up in non-ambulant boys with DMD.

Histology permits the observation of otherwise invisible structures of the internal topography of a specimen. Although it enables the investigation of tissues at a cellular level, it is invasive and breaks topology due to cutting. Three-dimensional (3D) reconstruction was thus introduced to overcome the limitations of single-section studies in a dimensional scope. 3D reconstruction finds its roots in embryology, where it enabled the visualisation of spatial relationships of developing systems and organs, and extended to biomedicine, where the observation of individual, stained sections provided only partial understanding of normal and abnormal tissues. However, despite bringing visual awareness, recovering realistic reconstructions is elusive without prior knowledge about the tissue shape. 3D medical imaging made such structural ground truths available. In addition, combining non-invasive imaging with histology unveiled invaluable opportunities to relate macroscopic information to the underlying microscopic properties of tissues through the establishment of spatial correspondences; image registration is one technique that permits the automation of such a process and we describe reconstruction methods that rely on it. It is thereby possible to recover the original topology of histology and lost relationships, gain insight into what affects the signals used to construct medical images (and characterise them), or build high resolution anatomical atlases. This paper reviews almost three decades of methods for 3D histology reconstruction from serial sections, used in the study of many different types of tissue. We first summarise the process that produces digitised sections from a tissue specimen in order to understand the peculiarity of the data, the associated artefacts and some possible ways to minimise them. We then describe methods for 3D histology reconstruction with and without the help of 3D medical imaging, along with methods of validation and some applications. We finally attempt to identify the trends and challenges that the field is facing, many of which are derived from the cross-disciplinary nature of the problem as it involves the collaboration between physicists, histolopathologists, computer scientists and physicians.

To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10−6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9–0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study

The design and operation of a facility in which a magnetic resonance imaging (MRI) scanner is incorporated into a room used for surgical or endovascular cardiac interventions presents several challenges. MR safety must be maintained in the presence of a much wider variety of equipment than is found in a diagnostic unit, and of staff unfamiliar with the MRI environment, without compromising the safety and practicality of the interventional procedure. Both the MR-guided cardiac interventional unit at Kings College London and the intraoperative imaging suite at the National Hospital for Neurology and Neurosurgery are single-room interventional facilities incorporating 1.5 T cylindrical-bore MRI scanners. The two units employ similar strategies to maintain MR safety, both in original design and day-to-day operational workflows, and between them over a decade of incident-free practice has been accumulated. This article outlines these strategies, highlighting both similarities and differences between the units, as well as some lessons learned and resulting procedural changes made in both units since installation.

Aim and objectives We aim to illustrate the diagnostic performance of diffusional kurtosis imaging (DKI) in the diagnosis of gliomas. Methods and materials A review protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P), registered in the international prospective register of systematic reviews, PROSPERO and published. Literature search in 4 databases was performed using the keywords “glioma” and “diffusional kurtosis”.After applying a robust inclusion/exclusion criteria, included articles were independently evaluated according to the QUADAS-2 tool.Data extraction was done in a pre-designed pro forma.Reported sensitivities and specificities were used to construct 2x2 tables and paired forest plots using the Review Manager (RevMan®) software.Random-effect model was pursued using the hierarchical summary receiver operator characteristics. Results Initially, 216 hits were retrieved. Considering duplicates and inclusion criteria; 23 articles were eligible for full-text reading. Ultimately, 19 studies were deemed to be eligible for final inclusion. Quality assessment revealed 9 studies with low risk of bias in the 4 domains. Using a bivariate random-effect model for data synthesis; summary ROC curve showed pooled area under the curve (AUC) of 0.92 and estimated sensitivity of 0.87 (95% CI: 0.78 - 0.92) in high/low grade gliomas’ differentiation.A mean difference in Mean Kurtosis (MK) value between HGG and LGG of 0.22 [95% CI: 0.25 - 0.19] was illustrated (p value = 0.0014) and a moderate degree of heterogeneity (I²= 73.8%). Conclusion DKI shows good diagnostic accuracy in high/low grade gliomas’ differentiation; which might qualify it to be part of the routine clinical practice, however; further evidence is deemed for technique standardization.

Purpose To compare the influence of two limb positions and slice prescription using scout-image–based and surface-anatomy–based methods on the reproducibility of quantitative MRI of lower-limb muscles. Materials and Methods Ten healthy subjects were scanned at 3 Tesla with a two-dimensional turbo spin-echo T1-weighted acquisition. Imaging was performed at thigh and calf level in two subject limb positions and independently repeated by a second operator. Regions-of-interest (ROI) were drawn on three muscles at thigh and calf levels on axial slices at fixed distance from the knee joint and at a level determined by surface anatomy. Results Test–retest reliability of muscle cross-sectional area and ROI area overlap were similar for both limb positioning methods. Changing limb position between scans reduced ROI overlap (P

We assessed the presence, frequency and pattern of MRI abnormalities in non-dystrophic myotonia patients. We reviewed T1-weighted and STIR (short-tau-inversion-recovery) 3T MRI sequences of lower limb muscles at thigh and calf level in 21 patients with genetically confirmed non-dystrophic myotonia: 11 with CLCN1 mutations and 10 with SCN4A mutations, and 19 healthy volunteers. The MRI examinations of all patients showed hyperintensity within muscles on either T1-weighted or STIR images. Mild extensive or marked T1-weighted changes were noted in 10/21 patients and no volunteers. Muscles in the thigh were equally likely to be affected but in the calf there was sparing of tibialis posterior. Oedema was common in calf musculature especially in the medial gastrocnemius with STIR hyperintensity observed in 18/21 patients. In 10/11 CLCN1 patients this included a previously unreported “central stripe”, also present in 3/10 SCN4A patients but no volunteers. Degree of fatty infiltration correlated with age (rho=0.46, p

Introduction Sensory ganglionopathies are uncommon but potentially very disabling. They have heterogeneous etiologies including autoimmune, paraneoplastic, toxic, and inflammatory although many remain idiopathic despite intensive investigation. Asymmetric sensory loss is relatively common at the onset, but with time, symptoms usually spread to involve all limbs symmetrically. Methods We report 6 patients with a persistent strikingly asymmetrical sensory ganglionopathy with acute or subacute onset and slow progression. Results Peripheral nerve biopsies in 5 patients showed axonal loss without significant inflammation; a dorsal root ganglion biopsy in 1 patient showed neuronal loss and inflammatory infiltrate. Four patients received immunomodulatory treatment, but overall the response to treatment was poor. Conclusions Asymmetrical sensory ganglionopathies may have an inflammatory basis. Immunomodulatory therapy may be considered early in the disease course, although in this series there was a limited response to treatment. Muscle Nerve, 2013